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评估益生菌对斑马鱼模型神经发育和行为反应的影响:对自闭症谱系障碍治疗的启示。

Assessment of Probiotics' Impact on Neurodevelopmental and Behavioral Responses in Zebrafish Models: Implications for Autism Spectrum Disorder Therapy.

作者信息

Bu Ling-Kang, Jia Pan-Pan, Huo Wen-Bo, Pei De-Sheng

机构信息

School of Public Health, Chongqing Medical University, Chongqing, 400016, China.

Chongqing Miankai Biotechnology Research Institute Co., Ltd., Chongqing, 400025, China.

出版信息

Probiotics Antimicrob Proteins. 2024 Aug 1. doi: 10.1007/s12602-024-10335-y.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder; the prevalence of which has been on the rise with unknown causes. Alterations in the gut-brain axis have been widely recognized in ASD patients, and probiotics are considered to potentially benefit the rescuing of autism-like behaviors. However, the effectiveness and mechanisms of multiple probiotics on zebrafish models are still not clearly revealed. This study aims to use the germ-free (GF) and conventionally raised (CR) AB wild-type zebrafish and the mutant Tbr1b and Katnal2 lines as human-linked ASD animal models to evaluate the effects of multiple probiotics on mitigating developmental and behavioral defects. Results showed that the addition of probiotics increased the basic important developmental indexes, such as body length, weight, and survival rate of treated zebrafish. Moreover, the Lactobacillus plantarum and Lactobacillus rhamnosus affected the behavior of CR zebrafish by increasing their mobility, lowering the GF zebrafish manic, and mitigating transgenic zebrafish abnormal behavior. Moreover, the expression levels of key genes related to gamma-aminobutyric acid (GABA), dopamine (DA), and serotonin (5-HT) as important neuropathways to influence the appearance and development of autism-related disorders, including gad1b, tph1a, htr3a, th, and slc6a3, were significantly activated by some of the probiotics' treatment at some extent. Taken together, this study indicates the beneficial effects of different probiotics, which may provide a novel understanding of probiotic function in related diseases' therapy.

摘要

自闭症谱系障碍(ASD)是一种神经发育障碍;其患病率一直在上升,病因不明。肠道-脑轴的改变在ASD患者中已得到广泛认可,益生菌被认为可能有助于挽救自闭症样行为。然而,多种益生菌对斑马鱼模型的有效性和机制仍未明确揭示。本研究旨在使用无菌(GF)和常规饲养(CR)的AB野生型斑马鱼以及突变的Tbr1b和Katnal2品系作为与人类相关的ASD动物模型,以评估多种益生菌对减轻发育和行为缺陷的影响。结果表明,添加益生菌增加了经处理斑马鱼的基本重要发育指标,如体长、体重和存活率。此外,植物乳杆菌和鼠李糖乳杆菌通过增加CR斑马鱼的活动能力、降低GF斑马鱼的狂躁程度以及减轻转基因斑马鱼的异常行为来影响其行为。此外,作为影响自闭症相关障碍出现和发展的重要神经通路,与γ-氨基丁酸(GABA)、多巴胺(DA)和5-羟色胺(5-HT)相关的关键基因,包括gad1b、tph1a、htr3a、th和slc6a3的表达水平,在一定程度上被某些益生菌处理显著激活。综上所述,本研究表明了不同益生菌的有益作用,这可能为益生菌在相关疾病治疗中的功能提供新的认识。

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